17-3467489-G-A

Variant names:

• chr17-3467489-G-A
• rs145051415
• NM_001170698.2:c.109C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170698.2(SPATA22):​c.109C>T​(p.Leu37Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

Genes affected

SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18801248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA22	NM_001170698.2	c.109C>T	p.Leu37Phe	missense_variant	Exon 3 of 9	ENST00000572969.6	NP_001164169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA22	ENST00000572969.6	c.109C>T	p.Leu37Phe	missense_variant	Exon 3 of 9	1	NM_001170698.2	ENSP00000460187.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250304 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135336

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458516 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;T;T;.;.;T;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	.;.;.;T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M;M;M;M;.;M;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;.;.;.;N;N;.;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D;.;.;.;T;D;.;.;.
Sift4G	Benign	0.068	T;T;T;T;D;D;.;D;.
Polyphen		0.99	D;D;D;D;D;.;.;.;.
Vest4		0.25
MutPred		0.11		Loss of catalytic residue at L37 (P = 0.0314);Loss of catalytic residue at L37 (P = 0.0314);Loss of catalytic residue at L37 (P = 0.0314);Loss of catalytic residue at L37 (P = 0.0314);Loss of catalytic residue at L37 (P = 0.0314);Loss of catalytic residue at L37 (P = 0.0314);.;Loss of catalytic residue at L37 (P = 0.0314);Loss of catalytic residue at L37 (P = 0.0314);
MVP		0.40
MPC		0.037
ClinPred		0.66	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145051415; hg19: chr17-3370783;